Sea snail venom could become the gold standard for the relief of nerve-related pain following the development of a pill that is 100 times as potent as leading treatments.

Current treatments for neuropathic pain include morphine, which is highly addictive, and gabapentin, which both act on nerve receptors. Sea snail venom had been suggested as a good alternative because it consists of a cocktail of peptides, known as conotoxins. These act to immobilise prey by blocking nerve-cell conduction, but in mammals the peptides are an effective analgesic.

The only conotoxin-derived drug approved for human use is ziconotide. Unfortunately, the drug is susceptible to breakdown by enzymes in the saliva and gut, so it is administered by a pump surgically inserted into the abdominal wall, making it an invasive and expensive treatment.

To solve this problem, David Craik and his team at the University of Queensland in Australia have developed the first "orally active" conotoxin drug.

They started with a synthetic version of conotoxin. Since the enzymes that break down the drug usually act at the ends of the conotoxin molecule, the team used a chain of amino acids to join up these ends to form a circular structure. They found this version to be resistant to enzymes in the body.

Craik's team tested the conotoxin in rats with neuropathic pain. They found that a single oral dose significantly reduced pain using a standard test – how much pressure the rat could withstand before withdrawing its paw. Compared with gabapentin, conotoxin was judged to be 100 times more potent.

Because the conotoxin is so powerful, only very small doses are needed, reducing the risk of side effects, says Craik. His team has applied for approval from the US Food and Drug Administration for a trial in humans.

Tuesday, June 15, 2010

Now in its 4th year, Arrowhead's Annual Pain Therapeutics Summit continues to attract both academic and industry leaders from around the globe to discuss pain management, preclinical and clinical development of new pain therapeutics, regulatory issues, commercialization of new pain therapies and various other topics integral to the field of pain therapeutics.

Friday, June 04, 2010

On September 3, 2010, IASP will hold the first International Pain Summit at the Palais des congrès de Montréal immediately following the 13th World Congress on Pain.

Background

Worldwide, there is increasing awareness of the human suffering, health care burden, and economic impact created by under-treated pain of all types, including acute pain, chronic pain, pain caused by health conditions such as cancer and HIV/AIDS, and pain caused by treatments such as surgery and radiotherapy.

Although medical science has the capacity to relieve most moderate to severe pain, over 80% of the world population in pain still have no access to appropriate analgesia, including access to potent opioids such as morphine. The World Health Organization (WHO) estimates that 5 billion people live in countries with low or no access to controlled medicines and have no or insufficient access to treatment for moderate to severe pain. The WHO Pain Relief Ladder recommends the administration of different types of analgesics based on the severity of the pain and relies on the permanent availability of opioid analgesics.

Chronic pain is a one of the most significant causes of suffering and disability worldwide, and a common symptom of both cancer and HIV/AIDS. Up to 70% of cancer patients suffer from pain and, among individuals living with HIV/AIDS, wide estimates of pain prevalence at all stages of infection have been reported. While pain prevalence is diminished among individuals on antiretroviral therapy, studies continue to document the under-treatment of pain, even among individuals being treated for HIV infection. Pain treatment is also related to gender, as HIV-infected women with pain are twice as likely to be under-treated as their male counterparts.

Pain has a profound impact on the quality of life and can have physical, psychological and social consequences. It can lead to reduced mobility and a consequent loss of strength, compromise the immune system and interfere with a person's ability to eat, concentrate, sleep, or interact with others as the physical and psychological effects of chronic pain influence the course of disease. Chronic pain can indirectly influence disease outcomes by reducing treatment adherence.

The International Pain Summit in Montréal will be the first global meeting about the crucial aspects of pain management, with a focus on advocacy and assistance for all countries to develop national pain strategies.

International Pain Summit Mission

We aim to improve the quality of life for people living with pain and to minimize the burden of pain on individuals and communities worldwide.

Goals

To develop a set of desirable characteristics of national pain strategies that can be agreed upon internationally. Individual countries can then use these broad principles to more fully develop specific strategies based on their own local requirements.

To gain the attention of communities, the media, and governments about the magnitude of the health and economic problem of untreated acute pain, chronic pain, and pain caused by cancer, HIV/AIDS, and other diseases and treatments.

To involve health ministers and other government officials in developing and implementing national pain strategies.

To begin to develop "best practice" models of service delivery.

To contribute to the destigmatization of chronic pain.

To draw further attention to pain relief as a fundamental human right.

To advocate for increased emphasis on and support of pain education and research.

Intended Audience and Participants

Leaders of current initiatives, including representatives from IASP's 84 national chapters

Senior Health Administrators and Ministers

Palliative Care Organizations

International Narcotics Control Board representatives

Human Rights advocates

World Health Organization (WHO)

National consumer (patient) organizations

International Media

Call for Action

The summit will end with:

Agreement on and signing of a declaration aimed at focusing world attention on under-treatment of all forms of pain, and

A call for equity of access to treatment as a moral imperative and to support pain management as a fundamental human right.

Registration

The cost of registration is CAD $75. This includes, in addition to the Pain Summit, coffee breaks and a box lunch. Space is limited to only 250 delegates, so be sure to register soon!

Thursday, June 03, 2010

People who meditate regularly find it easier to cope with pain because their brains anticipate it less, a study has found.

The findings could help develop new treatments from those who suffer from conditions that cause chronic pain.

Scientists from Manchester University compared non-meditators with a group who had meditated. Although they had varying levels of experience they had all tried mindfulness meditation, which seeks to anchor the person in the present.

Brain scans revealed that the most advanced meditators were the least likely to anticipate pain induced by a laser device, which made the experience more bearable.

Lead researcher Dr Christopher Brown, said: 'Meditation is becoming increasingly popular as a way to treat chronic illness such as the pain caused by arthritis.

'Recently, a mental health charity called for meditation to be routinely available on the NHS to treat depression, which occurs in up to 50 per cent of people with chronic pain.

'However, scientists have only just started to look into how meditation might reduce the emotional impact of pain.'

The study, to be published in the journal Pain, found that participants who meditated showed unusual activity in the brain region known to be involved in controlling attention and thought processes when potential threats are perceived.

'Meditation trains the brain to be more present-focused and therefore to spend less time anticipating future negative events. This may be why meditation is effective at reducing the recurrence of depression, which makes chronic pain considerably worse.'

Dr Brown said the findings should encourage further research into how the brain is changed by meditation practice.

He said: 'Although we found that meditators anticipate pain less and find pain less unpleasant, it's not clear precisely how meditation changes brain function over time to produce these effects.

'However, the importance of developing new treatments for chronic pain is clear: 40 per cent of people who suffer from chronic pain report inadequate management of their pain problem.'

In the UK, more than 10 million adults consult their GP each year with arthritis and related conditions. The estimated annual direct cost of these conditions to health and social services is £5.7billion.

Study co-author Professor Anthony Jones said: 'There may also be some types of patient with chronic pain who benefit more from meditation-based therapies than others.

'If we can find out the mechanism of action of meditation for reducing pain, we may be able to screen patients in the future for deficiencies in that mechanism, allowing us to target the treatment to those people.'

Wednesday, June 02, 2010

Most human vices have enough sense to be very, very tempting. Lust, gluttony, sloth, hurling powerful if unimaginative expletives at a member of the political opposition, buying a pair of Thierry Rabotin snakeskin printed shoes at 25 percent off even though you just bought a pair of cherry-red slingbacks last week — all these things feel awfully good to indulge in, which is why people must be repeatedly abjured not to.

One vice, however, dispenses with any hedonic trappings and instead feels so painful you would think it was a virtue, except that there's no gain in lean muscle mass at the end: envy. Skulking at sixth place on traditional lists of the seven deadly sins, right between wrath and pride, envy is the deep, often hostile resentment you feel toward somebody who has something you want, like wealth, beauty, a promotion or the admiration of peers. It is a vice few can avoid yet nobody craves, for to experience envy is to feel small and inferior, a loser shrink-wrapped in spite.

"Envy is corrosive and ugly, and it can ruin your life," said Richard H. Smith, a professor of psychology at the University of Kentucky who has written about envy. "If you're an envious person, you have a hard time appreciating a lot of the good things that are out there, because you're too busy worrying about how they reflect on the self."

Now researchers are gleaning insights into the neural and evolutionary underpinnings of envy, and why it can feel like a bodily illness or a physical blow. They're also tracing the pathway of envy's equally petty foil, the sensation of schadenfreude — taking pleasure when those whom you envied are themselves brought down low.

Reporting in the current issue of the journal Science, researchers at the National Institute of Radiological Sciences in Japan and their colleagues described brain-scanning studies of subjects who were told to imagine themselves as protagonists in social dramas with characters of greater or lesser status or achievement. When confronting characters that the participants admitted to envying, brain regions involved in registering physical pain were aroused: the higher the subjects rated their envy, the more vigorously flared the pain nodes in the brain's dorsal anterior cingulate cortex and related areas.

Conversely, the researchers said, when subjects were given a chance to imagine the golden one's downfall, the brain's reward circuits were activated, again in proportion to the strength of envy's sting: the subjects who felt the greatest envy the first time around reacted to news of their rival's misfortune with a comparatively livelier response in the dopamine-rich pleasure centers of, for example, the ventral striatum. "We have a saying in Japanese, 'The misfortunes of others are the taste of honey,' " said Hidehiko Takahashi, the first author on the report. "The ventral striatum is processing that 'honey.' "

Matthew D. Lieberman of the psychology department at the University of California, Los Angeles, who co-wrote a commentary that accompanies the report, said he was impressed by how the neural correlates of envy and schadenfreude were tied together, with the magnitude of one predicting the strength of the other. "This is the way other needs-processing systems like hunger and thirst work," he said. "The hungrier or thirstier that you feel, the more pleasurable it is when you finally eat or drink."

The new findings are preliminary, and some scientists have expressed reservations about what they or other scanning results from the fast-moving field of behavioral neuroscience really mean. Nevertheless, the research throws a spotlight on a potent emotion that we deny or deride but ignore at our peril. Much of the recent economic crisis, Dr. Smith suggested, may well have been fueled by runaway envy, as financiers competed to avoid the shame of being a "mere" millionaire.

Envy can be seen in other social animals with personal reputations to defend. Frans de Waal of the Yerkes National Primate Research Center in Atlanta noted that monkeys were perfectly happy to work for cucumber slices until a person started giving one monkey a preferred treat like grapes. Then the others stopped working for cucumbers and started nursing a grudge. "The underlying emotion is likely envy or resentment," Dr. de Waal said.

When children realize they have siblings, their lives become dominated by the calipers of envy. Why does she always get to sit by the window? His cupcake has more sprinkles! No siblings? No problem: you can envy the cat.

Researchers often distinguish between envy and the jealousy you feel by, say, seeing a loved one flirt at a party. Jealousy is a triangle, Dr. Smith said, in which you fear losing a loved one to the embrace of another. Envy is a two-bodied affair, an arrow proceeding from your covetous breast to the heart of the well-endowed Other. Yet envy is restless and gregarious and can embrace popular cliques, honor rolls and entire nation-states. "It's a fact of life that we pay close attention to status, to who's doing well and who isn't and how we stand in comparison to others," said Colin W. Leach, an associate professor of psychology at the University of Connecticut, in Storrs, who studies envy.

As a rule, we envy those who are like us in most ways — in sex, age, class and curriculum vitae. Potters envy potters, Aristotle observed.

Paradoxically, this most socially driven of emotions is among the least socially acceptable to confess to. Jealous hostility toward a romantic rival is an acceptable topic for conversation. Envious hostility toward a professional rival is more like an embarrassing body function: please do not share. When asked by researchers about their envy, study participants have said, "I'm privately ashamed of myself."

As evolutionary scientists see it, envy's salient features — its persistence and universality, its fixation with social status and the fact that it cohabits with shame — suggest that it serves a deep social role. They propose that our invidious impulses may help explain why humans are comparatively less hierarchical than many primate species, more prone to a rough egalitarianism and to rebelling against kings and tycoons who hog more than their fair share.

Envy may also help keep us in line, making us so desperate to look good that we take the high road and start to act good, too. We struggle with our private envy, our longing for more esteem than we command, and the struggle only sharpens the painful contrast between the imagined perfection of the envied adversary that we have enshrined on an imaginary throne, and the defective merchandise that is ourselves.

"If you desire glory, you may envy Napoleon," Bertrand Russell said. "But Napoleon envied Caesar, Caesar envied Alexander, and Alexander, I daresay, envied Hercules, who never existed." If envy is a tax levied by civilization, it is one that everyone must pay.

Tuesday, June 01, 2010

The goal of this FOA is to facilitate the partnering of pain scientists and non-pain neuroscientists to capture insights and expertise from disciplines where transitions from health to disease have been extensively examined. An expected outcome of this FOA will be the formation of partnerships between pain researchers and non-pain neuroscientists to develop a new collaboration focused on understanding the maladaptive neuroplastic changes that occur during the transition from acute to chronic neuropathic pain. It is anticipated that these initial collaborations will lead to new applications for highly innovative projects centered on similar studies of the transition from acute to chronic pain. The purpose of this FOA is to encourage the submission of competitive revision applications that propose a collaborative, one year pilot study or a new specific aim associated with an active NIH grant. The parent grant may be focused on pain or on neural plasticity outside the area of pain. Chronic neuropathic pain conditions are difficult to treat and we currently lack an understanding of the mechanisms underlying the transition to a chronic pain state after acute nerve injury. It is hypothesized that those individuals transitioning to a chronic pain state after acute injury undergo a maladaptive neuroplastic process in contrast to those who recover from injury without chronic pain. The application of expertise, tools, and knowledge from the field of neural plasticity will bring new insights and approaches to elucidate the changes associated with onset and maintenance of pain chronicity. New knowledge garnered from these studies will enable improved diagnosis, prevention, and treatment of chronic neuropathic pain conditions.

Pain conditions are a major health problem in the US and their economic burden approaches $100 billion per year in lost productivity and medical expenses. These conditions lead to medical morbidity and a reduced quality of life for millions of Americans. Chronic neuropathic pain conditions are especially difficult to treat. We currently have a relatively incomplete understanding of the etiology and pathology of chronic neuropathic pain conditions. A largely unaddressed challenge is our lack of knowledge in determining who will transition to a chronic pain state and how to treat patients to prevent this transition. We need to understand, mechanistically, how pain changes from an acute, high threshold, protective response to a chronic, low threshold, and spontaneous dysfunctional condition. While most researchers believe that the transition from acute to chronic neuropathic pain is the result of maladaptive plasticity in the nervous system, we do not fully understand how acute pain progresses to chronic pain at any level, from the molecular to systems. In contrast, other neuroscience researchers have made extraordinary strides in delineating the neuroplastic changes that occur in cognitive decline, in developmental disorders, and in addiction. Our understanding of the molecular and cellular mechanisms surrounding normal adaptive responses and maladaptive changes in cognition, neurodevelopment, aging, neurodegeneration, and the stress response has increased. Neuroscientists have a detailed knowledge of synaptic plasticity in the hippocampus that leads to long-term memory formation. The close linkage between the neuroplastic changes that are induced by chronic stress and the reversal of these changes by antidepressant drug therapy has been extensively studied by neuroscientists studying mood disorders. These discoveries have been aided by the application of novel molecular, electrophysiological, imaging, and genetic technologies. There is a real opportunity for neuroscientists in these related fields to apply their expertise, techniques, and extensive knowledge of neuroplasticity to pain research. Our understanding of the neuroplastic changes that occur in the dorsal horn of the spinal cord and in the brain when patients transition to a chronic pain state will be enhanced by the participation of these researchers in chronic pain studies.

Research supported by this program will lead to the development of a detailed molecular, cellular, and systems level understanding of the neurobiological basis of the transition from acute to chronic pain. In this regard it is critical to understand the mechanisms underlying the neuroplasticity mediating the increased sensitivity to noxious and innocuous stimuli and the amplification of pain signaling in chronic pain patients. In addition, a detailed picture of the changes in the nociceptive circuits in the brain and dorsal horn of the spinal cord and the chemical, functional, and structural alterations that occur during the transition to chronic pain will need to be delineated. Identification and manipulation of the neuroanatomical hubs of integration of pain signaling and altered activity are critical steps in moving towards prevention and treatment of chronic pain. The identification of crucial steps in altered pain signaling will provide opportunities to prevent or reverse changes that lead to persistent pain.

The overall objectives of this FOA are to 1) expand the scope of the parent grant to apply advances in our understanding of neural plasticity in non-pain systems to pain pathways and 2) expand the pool of investigators in pain research in order to bring additional expertise and cutting edge technologies in neural plasticity into the pain field.

The programmatic focus for these competitive revisions is maladaptive neuroplasticity in pain pathways and the transition from acute to chronic pain. A broad array of research and experimental approaches are being sought that will center on nervous system plasticity. The research may be hypothesis driven or discovery science. Research approaches may include, but are not limited to molecular, cell biological, animal, behavioral, or systems approaches. Experimental approaches may include, but are not limited to biochemical, immunocytochemical, morphometric, and electrophysiological analyses; molecular, cellular, and functional imaging; genomic, proteomic, and metabolomic analyses; neuronal circuit mapping and manipulation; development of new animal models of neuropathic pain; development of new behavioral and functional assays ofpain, and identification of biobehavioral mechanisms including mediating and moderating variables that may influence the transition from acute to chronic pain.

Principal Investigators should clearly describe how the expertise or technology provided by the collaboration between the pain and non-pain scientist will provide a novel scientific approach to the existing project. In addition, the PI should describe how this collaboration will provide the basis for future grant applications that expand upon one of the current projects or lead to an entirely new approach to chronic neuropathic pain research.